Construct indeno[1,2-b]oxepine or cis-cyclopropylacrylate by sulfur ylides.

For the first time, the [4 + 3] or [2 + 1] annulation of crotonate-derived sulfur ylides with arylidenemalononitrile or arylidene-1H-indene-1,3(2H)-dione is reported using Na2CO3 as the base. This protocol is advantageous as it does not require prior preparation of arylidenemalononitrile or arylidene-1H-indene-1,3(2H)-dione substrates, due to the independent participation of the base in the two reactions. This mild, operationally multicomponent process can be employed for the transformation of a wide variety of commercially available aldehydes into the corresponding indeno[1,2-b]oxepine or cyclopropyl acrylate core in moderate to excellent yields under mild conditions. This journal is © The Royal Society of Chemistry.

Introduction

Oxygen-containing heterocyclic compounds, especially unsaturated 7-membered oxacycle (oxepine) frameworks, exhibit a wide range of biological properties, such as ion-channel blocking, antiplasmodial, antiviral, antipsychotic, and antifungal activities.[1] Various natural and marine natural products containing the oxepine motif play a vital role in biological processes.[2] The cyclopropyl group is also a vital structural unit in several synthetic and naturally occurring compounds, exhibiting a wide spectrum of biological properties ranging from enzyme inhibition to herbicidal, antibiotic, antitumor, and antiviral activities.[3]Fig. 1 shows some representative examples of these compounds.

Fig. 1

Biologically active substances containing oxepine motif and cyclopropyl.

Recently, crotonate-derived sulfur ylides have attracted attention in organic synthesis as sources of one-carbon or three-carbon synthons in the presence of an inorganic base.[4] The ability of crotonate-derived sulfur ylides to undergo [m + n] cycloaddition reactions with various substrates is exploited to construct several cyclic compounds.[5] Tang and co-workers have synthesized vinylaziridine by the diastereoselective annulation of crotonate-derived sulfur ylides with cyclic ketamine (Scheme 1a).[6] Huang and co-workers have reported access to cyclic 2-alkenyl aziridines by sequential annulation using crotonate-derived sulfur ylides as the C3 synthon with α,β-unsaturated cyclic ketimines (Scheme 1b).[5] Huang has synthesized seven-membered nitrogen-heterocycles with moderate-to-excellent yields by the development of a novel [4 + 3] annulation of azadienes with crotonate sulfonium salts (Scheme 1c).[8] On the other hand, multicomponent reactions (MCRs), defined as processes that combine at least three reactants in the same pot to generate a product containing most of the atoms of the starting material, have been extensively exploited to prepare small molecules with step economy, energy conservation, and emission reduction.[9] As highly reactive reagents, sulfur ylides can react with various electrophiles such as aldehydes, imines, and electron-deficient alkenes.[10] Therefore, the design of MCRs involving sulfur ylides in the presence of aldehydes, 1,3-indanedione, and malononitrile might lead to selectivity problems.

Scheme 1

Annulation with crotonate-derived sulfur-ylides.

Despite these challenges, it is interesting to develop sulfur ylide-mediated MCRs to construct core structures with medicinal interest. Based on the aforementioned motivation and our continued interest in organocatalysis, herein, the construction of indeno[1,2-b]oxepine by the three-component [4 + 3] or [1 + 2] annulation of crotonate-derived sulfur ylides, aldehydes, and 1,3-indanedione or malononitrile (Scheme 1d).

Results and discussion

Prior to investigation of the desired MCRs and sulfur ylides, studies were first initiated by investigating reactions between crotonate sulfonium salt 3a and 2-benzylidene-1H-indene-1,3(2H)-dione, which was generated by the reaction of 1,3-indanedione (1a) and benzaldehyde (2a) (Table 1). The reaction was performed in DCM with NaHCO3 as the base at 25 °C (Table 1, entry 1). Gratifyingly, the [4 + 3] annulation product was obtained in 76% yield. The structure of 4a was confirmed by NMR and HRMS. Reaction conditions were optimized to improve the product yield. Optimization of base was first carried out. When the reaction was conducted in t-BuOK, the yield was improved to 85% (Table 1, entry 2). Moderate product yields were observed by using other bases, such as DABCO, TMAF, Cs2CO3, NaOH, Et3N, K2CO3 and K3PO4 (Table 1, entries 3–9). To our surprise, the product yield was improved to 90% when the base was used instead of Na2CO3. Although NaH was also found to afford yields similar to that obtained using Na2CO3, the cost-effective base was used for [4 + 3] cyclization (Table 1, entries 10 and 11). After the optimization of the base, the scope of different solvents for the was investigated. Common solvents (CH3CN, CH3OH, THF, toluene, DCE) failed to further improve the product yields (Table 1, entries 12–16). In addition, the reaction temperature significantly affected the reaction. By decreasing the temperature from room temperature to 0 °C, the product yield decreased from 90% to 45% even for a longer reaction time of 6 h (Table 1, entry 17). Neither the decrease nor increase the temperature led to the improvement of the yield of 4a (Table 1, entries 17 and 18).

Optimization of the MCRs reactiona

Entry	Base	Solvent	Temp (°C)	Yieldb (%)
1	NaHCO3	DCM	25	76
2	t-BuOK	DCM	25	85
3	DABCO	DCM	25	75
4	TMAF	DCM	25	76
5	Cs2CO3	DCM	25	56
6	NaOH	DCM	25	73
7	Et3N	DCM	25	70
8	K2CO3	DCM	25	79
9	K3PO4	DCM	25	50
10	NaH	DCM	25	90
11	Na 2 CO 3	DCM	25	90
12	Na2CO3	CH3CN	25	79
13	Na2CO3	CH3OH	25	48
14	Na2CO3	THF	25	55
15	Na2CO3	Toluene	25	67
16	Na2CO3	DCE	25	70
17	Na2CO3	DCM	0	45
18	Na2CO3	DCM	60	88

Unless otherwise specified, the reactions were carried out with 1a (0.2 mmol), 2a (0.24 mmol) and 3a (0.3 mmol) in the presence of base (0.4 mmol) in a solvent (2 mL) at 25 °C.

Isolated yield.

Using optimized reaction conditions (Table 1, entry 11), the substrate scope of the substituted benzaldehydes was first investigated (Scheme 2). Different benzaldehydes with a variety of functional groups such as NO2, CN, Cl, CH3, N(CH3)2, and OCH3 smoothly reacted with 1a and 3a to afford the corresponding indeno[1,2-b]oxepine (4b–4o) in moderate to excellent yields (42–90%), thus offering a broad range of opportunities for further derivatization. These results revealed that reactions of benzaldehydes bearing electron-donating and electron-withdrawing groups at the para position do not clearly affect this transformation. In particular, aromatic aldehydes bearing a functional group at the para position exhibited higher reactivity than their ortho- or meta-substituted counterpart (4gvs.4h and 4j). However, for polysubstituted aromatic aldehydes, yields for the desired products were less (4k, 4o) than those for the monosubstituted aromatic aldehydes. In addition, the structure of 4o was further confirmed by single-crystal X-ray analysis.[11] Moreover, reactions efficiently proceeded when sulfonium salt 3b was used, affording desired products in moderate to excellent yields (4l–4n). As expected, heteroaryl aldehydes, such as 5-methylfurfural, furfural, 2-thenaldehyde, and nicotinaldehyde, performed quite well in the MCRs (4p–4s). The use of indole-3-carboxaldehyde afforded low yields of the desired product (4t). However, when indole-3-carboxaldehyde was protected using iodomethane, the product yield was increased to 70% (4u).

Scheme 2

Scope of the [4 + 3] reactions.Unless otherwise specified, the reactions were carried out with 1 (0.2 mmol), 2a (0.24 mmol) and 3 (0.3 mmol) in the presence of base (0.4 mmol) in a solvent (2 mL) at 25 °C. Isolated yield. The reaction was carried out at 0 °C.

To demonstrate the generality of this transformation, malononitrile was investigated instead of 1,3-indanedione under the optimal conditions. As shown in Scheme 3, electron-withdrawing or electron-donating groups such as nitro, cyano and N,N-dimethyl, at the para-position R1 in the substrate 2 smoothly reacted with 5a and 3a to afford [2 + 1] annulation products 6a–6d (69–89%) with an excellent cis/trans ratio. To our delight, the desired cis-cyclopropylacrylate 6a was still exclusively obtained (cis/trans >99/1) in 80% yield using 1.0 mmol of substrate 5a. While the methoxy group substituted at the meta position in 6e afforded low product yield (75%), the structure of 6e was further confirmed by single-crystal X-ray analysis.[12] However, for polysubstituted aromatic aldehydes, the yield of the desired product 6f was less than that of the monosubstituted aromatic aldehyde. As expected, heteroaryl aldehydes, such as 5-methylfurfural, furfural, 2-thenaldehyde, nicotinaldehyde, and 1-methyl-1H-indole-3-carbaldehyde performed quite well in the MCRs (6g–6k). In addition, aliphatic aldehydes proved to be suitable substrates to furnish the desired reaction in moderate yields (6l, 57%). Moreover, reactions proceeded efficiently proceeded when sulfonium salt 3b was used, affording desired products in moderate to excellent yields (6m–6o, 6q). Furthermore, cyanoacrylates also afforded the desired products (6o–6q). The relative configuration of 6o was defined on the basis of the phase-sensitive NOESY spectrum. No correlation between hydrogen on cyclopropane and methyl by the NOESY spectrum was observed (see the ESI†).

Scheme 3

Scope of the [2 + 1] reactions.Unless otherwise specified, the reactions were carried out with 5 (0.2 mmol), 2 (0.24 mmol) and 3 (0.3 mmol) in the presence of base (0.4 mmol) in a solvent (2 mL) at 25 °C. Isolated yield.

Based on the present experimental data and the results described in the literature,[4] a plausible MCR reaction mechanism can be proposed as shown in Scheme 4. Crotonate-derived ylide 2 was treated with base (Na2CO3) to afford allylic ylide A, which resonated to B. Next, the Michael addition of B to C, which was formed by 1a and 2 in the presence of the base catalyst, afforded intermediate D. Intermediate D subsequently transformed into intermediate Gvia two proton-transfer processes, followed by an intramolecular SN2 nucleophilic substitution to furnish [4 + 3] annulation product 4. When we 5 was used instead of 1a, the Michael addition of A to I in the presence of the base catalyst would lead to intermediate J. Then, the subsequent intramolecular nucleophilic addition and elimination of Me2S further afforded the final product.

Scheme 4

Plausible reaction mechanism.

Conclusions

To the best of our knowledge, for the first time, a novel Na2CO3-promoted MCR reaction using crotonate-derived sulfonium salts, aromatic aldehydes, and 1,3-indanedione or malononitrile was developed. Various indeno[1,2-b]oxepine and cis-cyclopropylacrylate derivatives were obtained in good-to-excellent yields. The advantages of the current protocol included readily available starting materials, mild reaction conditions, good functional group tolerance, and broad substrate scope. Currently, further applications of this MCR reaction in organic synthesis, as well as investigations on the detailed mechanism, are underway in our laboratory.

Experimental section

General information

Infrared spectra were obtained on a FTIR spectrometer. 1H NMR and 13C NMR spectra were recorded on Agilent DD2400 spectrometer. CDCl3 was used as solvent. Chemical shifts were referenced relative to residual solvent. Melting points were measured with micro melting point apparatus. Infrared spectra were recorded on a FT-IR spectrometer. 1a, 2 and 5 were prepared from Energy Chemical. 3 were prepared according to the literature procedure.[14]

Experimental procedures and characterization date

Ethyl-6-oxo-5-phenyl-5,6-dihydro-2H-indeno[1,2-b]oxepine-4-carboxylate (4a)

In a 5 mL vial, 1,3-dioxo-2,3-dihydro-1H-inden-2-ylium 1a (29.2 mg, 0.2 mmol, 1.0 equiv.), (E)-(4-ethoxy-4-oxobut-2-en-1-yl)dimethylsulfonium bromide 3a (76.5 mg, 1.5 equiv.), Na2CO3 (42 mg, 2 equiv.) and l-proline (2.3 mg, 0.1 equiv.) was added. To this resultant mixture, benzaldehyde 2a (25.4 mg, 1.2 equiv.) and DCM (2 mL) were added and stirred at room temperature overnight. The reaction was confirmed by TLC. Then the solution was diluted with ethyl acetate and transferred to a round bottom flask. Silica gel was added to the flask and volatiles were evaporated under vacuum. The purification was performed by flash column chromatography on silica gel using ethyl acetate/petroleum ether (v/v, 1 : 10) as eluent to give 4a as a Yellow solid (62.3 mg, 90% yield), Rf = 0.21 (EtOAc/petroleum ether 1 : 10). Mp 115 °C; 1H NMR (CDCl3, 400 MHz), δ: 7.36 (d, J = 6.8 Hz, 1H), 7.28–7.16 (m, 6H), 7.12–7.05 (m, 3H), 5.29 (s, 1H), 4.83 (dd, J1 = 12.4 Hz, J2 = 7.6 Hz, 1H), 4.54 (dd, J1 = 12.4 Hz, J2 = 7.6 Hz, 1H), 4.28–4.16 (m, 2H), 1.25 (t, J = 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3), δ: 194.3, 173.6, 166.1, 144.5, 141.9, 139.7, 132.5, 132.1, 131.3, 130.0, 128.6, 127.1, 126.7, 121.3, 118.4, 109.6, 65.1, 61.8, 35.5, 14.3. IR(KBr) ν: 2974, 2918, 1712, 1628, 1579, 1460, 1397, 1243, 1095, 1046. HRMS(EI) (m/z): calcd for C22H18O4 (M + H)+: 347.1278; found: 347.1276.

Ethyl-5-(4-nitrophenyl)-6-oxo-5,6-dihydro-2H-indeno[1,2-b]oxepine-4-carboxylate (4b)

In a 5 mL vial, 1,3-dioxo-2,3-dihydro-1H-inden-2-ylium 1a (29.2 mg, 0.2 mmol, 1.0 equiv.), (E)-(4-ethoxy-4-oxobut-2-en-1-yl)dimethylsulfonium bromide 3a (76.5 mg, 1.5 equiv.), Na2CO3 (42 mg, 2 equiv.) and l-proline (2.3 mg, 0.1 equiv.) was added. To this resultant mixture, 4-nitrobenzaldehyde 2b (36.2 mg, 1.2 equiv.) and DCM (2 mL) were added and stirred at room temperature overnight. The reaction was confirmed by TLC. Then the solution was diluted with ethyl acetate and transferred to a round bottom flask. Silica gel was added to the flask and volatiles were evaporated under vacuum. The purification was performed by flash column chromatography on silica gel using ethyl acetate/petroleum ether (v/v, 1 : 5) as eluent to give 4b as a yellow solid (32.8 mg, 42% yield), Rf = 0.12 (EtOAc/petroleum ether 1 : 10). Mp 115 °C; 1H NMR (CDCl3, 400 MHz), δ: 8.15 (t, 1H), 8.13 (t, 1H), 7.52–7.47 (m, 3H), 7.39 (t, J = 8.0 Hz, 1H), 7.33 (t, J = 8.0 Hz, 1H), 7.25–7.20 (m, 2H), 5.42 (s, 1H), 4.80 (dd, J1 = 12.8 Hz, J2 = 7.2 Hz, 1H), 4.74–4.69 (m, 1H), 4.39–4.26 (m, 2H), 1.35 (t, J = 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3), δ: 194.2, 174.1, 165.8, 149.5, 146.8, 143.4, 139.4, 132.8, 132.8, 131.1, 130.5, 128.2, 123.9, 121.6, 118.9, 108.4, 65.2, 62.2, 35.9, 14.3. IR(KBr) ν: 2925, 2855, 1712, 1628, 1523, 1474, 1355, 1116, 990. HRMS(EI) (m/z): calcd for C22H17NO6 (M + H)+: 392.1129; found: 392.1128.

Ethyl-5-(4-cyanophenyl)-6-oxo-5,6-dihydro-2H-indeno[1,2-b]oxepine-4-carboxylate (4c)

In a 5 mL vial, 1,3-dioxo-2,3-dihydro-1H-inden-2-ylium 1a (29.2 mg, 0.2 mmol, 1.0 equiv.), (E)-(4-ethoxy-4-oxobut-2-en-1-yl)dimethylsulfonium bromide 3a (76.5 mg, 1.5 equiv.), Na2CO3 (42 mg, 2 equiv.) and l-proline (2.3 mg, 0.1 equiv.) was added. To this resultant mixture, 4-formylbenzonitrile 2c (31.4 mg, 1.2 equiv.) and DCM (2 mL) were added and stirred at room temperature overnight. The reaction was confirmed by TLC. Then the solution was diluted with ethyl acetate and transferred to a round bottom flask. Silica gel was added to the flask and volatiles were evaporated under vacuum. The purification was performed by flash column chromatography on silica gel using ethyl acetate/petroleum ether (v/v, 1 : 10) as eluent to give 4c as a yellow solid (45.3 mg, 61% yield), Rf = 0.15 (EtOAc/petroleum ether 1 : 10). Mp 132 °C; 1H NMR (CDCl3, 400 MHz), δ: 7.57 (d, 2H), 7,46–7.44 (m, 3H), 7.37 (t, J = 7.2 Hz, 1H), 7.32 (d, J = 8.0 Hz, 1H), 7.21 (t, J = 8.0 Hz, 2H), 5.38 (s, 1H), 4.81–4.76 (m, 1H), 4.72–4.67 (m, 1H), 4.37–4.24 (m, 2H), 1.34 (t, J = 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3), δ: 194.2, 174.1, 165.8, 147.4, 143.4, 139.4, 132.8, 132.7, 132.5, 131.0, 130.4, 128.1, 121.5, 118.9, 118.8, 110.7, 108.3, 65.2, 62.1, 35.9, 14.3. IR(KBr) ν: 2981, 2918, 2231, 1705, 1621, 1515, 1452, 1396, 1242, 1179, 1102, 1046. HRMS(EI) (m/z): calcd for C23H17NO4 (M + H)+: 372.1230; found: 372.1231.

Ethyl-5-(4-chlorophenyl)-6-oxo-5,6-dihydro-2H-indeno[1,2-b]oxepine-4-carboxylate (4d)

In a 5 mL vial, 1,3-dioxo-2,3-dihydro-1H-inden-2-ylium 1a (29.2 mg, 0.2 mmol, 1.0 equiv.), (E)-(4-ethoxy-4-oxobut-2-en-1-yl)dimethylsulfonium bromide 3a (76.5 mg, 1.5 equiv.), Na2CO3 (42 mg, 2 equiv.) and l-proline (2.3 mg, 0.1 equiv.) was added. To this resultant mixture, 4-chlorobenzaldehyde 2d (33.6 mg, 1.2 equiv.) and DCM (2 mL) were added and stirred at room temperature overnight. The reaction was confirmed by TLC. Then the solution was diluted with ethyl acetate and transferred to a round bottom flask. Silica gel was added to the flask and volatiles were evaporated under vacuum. The purification was performed by flash column chromatography on silica gel using ethyl acetate/petroleum ether (v/v, 1 : 10) as eluent to give 4d as a yellow solid (63.1 mg, 83% yield), Rf = 0.21 (EtOAc/petroleum ether 1 : 10). Mp 108 °C; 1H NMR (CDCl3, 400 MHz), δ: 7.45 (d, J = 7.2 Hz, 1H), 7.35 (t, J = 8.4 Hz, 1H), 7.28 (t, J = 7.6 Hz, 1H), 7.25–7.22 (m, 4H), 7.19–7.15 (m, 2H), 5.31 (s, 1H), 4.89–4.84 (m, 1H), 4.69–4.64 (m, 1H), 4.35–4.25 (m, 2H), 1.33 (t, J = 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3), δ: 194.3, 173.8, 166.0, 144.1, 140.5, 139.6, 132.6, 132.6, 132.3, 131.2, 130.2, 128.7, 128.6, 121.4, 118.6, 109.1, 65.1, 62.0, 35.2, 14.3. IR(KBr) ν: 2918, 1705, 1628, 1585, 1410, 1235, 1172, 1109, 1039, 955, 906, 765, 730. HRMS(EI) (m/z): calcd for C22H17ClO4 (M + H)+: 381.0888; found: 381.0890.

Ethyl-6-oxo-5-(p-tolyl)-5,6-dihydro-2H-indeno[1,2-b]oxepine-4-carboxylate (4e)

In a 5 mL vial, 1,3-dioxo-2,3-dihydro-1H-inden-2-ylium 1a (29.2 mg, 0.2 mmol, 1.0 equiv.), (E)-(4-ethoxy-4-oxobut-2-en-1-yl)dimethylsulfonium bromide 3a (76.5 mg, 1.5 equiv.), Na2CO3 (42 mg, 2 equiv.) and l-proline (2.3 mg, 0.1 equiv.) was added. To this resultant mixture, 4-methylbenzaldehyde 2e (28.8 mg, 1.2 equiv.) and DCM (2 mL) were added and stirred at room temperature overnight. The reaction was confirmed by TLC. Then the solution was diluted with ethyl acetate and transferred to a round bottom flask. Silica gel was added to the flask and volatiles were evaporated under vacuum. The purification was performed by flash column chromatography on silica gel using ethyl acetate/petroleum ether (v/v, 1 : 10) as eluent to give 4e as a Yellow oil (59.8 mg, 83% yield), Rf = 0.18 (EtOAc/petroleum ether 1 : 10). 1H NMR (CDCl3, 400 MHz), δ: 7.45 (d, J = 6.8 Hz, 1H), 7.37–7.33 (m, 1H), 7.31–7.27 (m, 1H), 7.22–7.13 (m, 4H), 7.08 (d, J = 8.0 Hz, 2H), 5.33 (s, 1H), 4.95 (dd, J1 = 12.4 Hz, J2 = 7.2 Hz, 1H), 4.63 (dd, J1 = 12.4 Hz, J2 = 8.0 Hz, 1H), 4.36–4.24 (m, 2H), 2.29 (s, 3H), 1.34 (t, J = 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3), δ: 194.4, 173.6, 166.2, 144.6, 139.8, 138.9, 136.3, 132.5, 132.0, 131.3, 130.0, 129.3, 127.1, 121.3, 118.4, 109.8, 65.2, 61.8, 35.3, 21.0, 14.3. IR(KBr) ν: 2911, 2855, 1712, 1628, 1508, 1466, 1403, 1235, 1109, 1039. HRMS(EI) (m/z): calcd for C23H20O4 (M + H)+: 361.1434; found: 361.1436.

Ethyl-5-(4-(dimethylamino)phenyl)-6-oxo-5,6-dihydro-2H-indeno[1,2-b]oxepine-4-carboxylate (4f)

In a 5 mL vial, 1,3-dioxo-2,3-dihydro-1H-inden-2-ylium 1a (29.2 mg, 0.2 mmol, 1.0 equiv.), (E)-(4-ethoxy-4-oxobut-2-en-1-yl)dimethylsulfonium bromide 3a (76.5 mg, 1.5 equiv.), Na2CO3 (42 mg, 2 equiv.) and l-proline (2.3 mg, 0.1 equiv.) was added. To this resultant mixture, 4-(dimethylamino)benzaldehyde 2f (35.8 mg, 1.2 equiv.) and DCM (2 mL) were added and stirred at room temperature overnight. The reaction was confirmed by TLC. Then the solution was diluted with ethyl acetate and transferred to a round bottom flask. Silica gel was added to the flask and volatiles were evaporated under vacuum. The purification was performed by flash column chromatography on silica gel using ethyl acetate/petroleum ether (v/v, 1 : 5) as eluent to give 4f as a yellow oil (68.5 mg, 88% yield), Rf = 0.15 (EtOAc/petroleum ether 1 : 10). 1H NMR (CDCl3, 400 MHz), δ: 7.44 (d, J = 7.2 Hz, 1H), 7.37–7.33 (m, 1H), 7.29 (d, J = 8.0 Hz, 1H), 7.21–7.09 (m, 4H), 6.65 (d, J = 8.8 Hz, 2H), 5.27 (s, 1H), 5.01 (dd, J1 = 12.4 Hz, J2 = 7.3 Hz, 1H), 4.63 (dd, J1 = 12.4 Hz, J2 = 7.8 Hz, 1H), 4.35–4.23 (m, 2H), 2.89 (s, 6H), 1.33 (t, J = 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3), δ: 194.5, 173.4, 166.4, 149.5, 144.9, 140.0, 132.5, 131.8, 131.4, 129.9, 129.7, 127.9, 121.2, 118.3, 112.8, 110.3, 65.3, 61.8, 40.8, 34.9, 14.4. IR(KBr) ν: 2911, 2841, 1705, 1628, 1515, 1473, 1403, 1340, 1228, 1109, 1046. HRMS(EI) (m/z): calcd for C24H23NO4 (M + H)+: 390.1700; found: 390.1699.

Ethyl-5-(4-methoxyphenyl)-6-oxo-5,6-dihydro-2H-indeno[1,2-b]oxepine-4-carboxylate (4g)

In a 5 mL vial, 1,3-dioxo-2,3-dihydro-1H-inden-2-ylium 1a (29.2 mg, 0.2 mmol, 1.0 equiv.), (E)-(4-ethoxy-4-oxobut-2-en-1-yl)dimethylsulfonium bromide 3a (76.5 mg, 1.5 equiv.), Na2CO3 (42 mg, 2 equiv.) and l-proline (2.3 mg, 0.1 equiv.) was added. To this resultant mixture, 4-methoxybenzaldehyde 2g (32.6 mg, 1.2 equiv.) and DCM (2 mL) were added and stirred at room temperature overnight. The reaction was confirmed by TLC. Then the solution was diluted with ethyl acetate and transferred to a round bottom flask. Silica gel was added to the flask and volatiles were evaporated under vacuum. The purification was performed by flash column chromatography on silica gel using ethyl acetate/petroleum ether (v/v, 1 : 10) as eluent to give 4g as a Yellow oil (64.7 mg, 86% yield), Rf = 0.18 (EtOAc/petroleum ether 1 : 10). 1H NMR (CDCl3, 400 MHz), δ: 7.44 (d, J = 7.2 Hz, 1H), 7.35 (t, J = 7.6 Hz, 1H), 7.29 (t, J = 8.0 Hz, 1H), 7.24 (d, J = 9.2 Hz, 2H), 7.18–7.12 (m, 2H), 6.81 (d, J = 8.8 Hz, 2H), 5.30 (s, 1H), 4.95 (dd, J1 = 12.4 Hz, J2 = 7.2 Hz, 1H), 4.64 (dd, J1 = 12.4 Hz, J2 = 8.0 Hz, 1H), 4.36–4.24 (m, 2H), 3.76 (s, 3H), 1.34 (t, J = 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3), δ: 194.4, 173.6, 166.2, 158.4, 144.7, 139.9, 134.0, 132.5, 132.0, 131.3, 130.1, 128.3, 121.3, 118.4, 114.0, 109.9, 65.2, 61.8, 55.4, 35.0, 14.3. IR(KBr) ν: 2925, 1712, 1628, 1515, 1466, 1403, 1249, 1179, 1102, 1039. HRMS(EI) (m/z): calcd for C23H20NO5 (M + H)+: 377.1384; found: 377.1385.

Ethyl-5-(3-methoxyphenyl)-6-oxo-5,6-dihydro-2H-indeno[1,2-b]oxepine-4-carboxylate (4h)

In a 5 mL vial, 1,3-dioxo-2,3-dihydro-1H-inden-2-ylium 1a (29.2 mg, 0.2 mmol, 1.0 equiv.), (E)-(4-ethoxy-4-oxobut-2-en-1-yl)dimethylsulfonium bromide 3a (76.5 mg, 1.5 equiv.), Na2CO3 (42 mg, 2 equiv.) and l-proline (2.3 mg, 0.1 equiv.) was added. To this resultant mixture, 3-methoxybenzaldehyde 2h (32.6 mg, 1.2 equiv.) and DCM (2 mL) were added and stirred at room temperature overnight. The reaction was confirmed by TLC. Then the solution was diluted with ethyl acetate and transferred to a round bottom flask. Silica gel was added to the flask and volatiles were evaporated under vacuum. The purification was performed by flash column chromatography on silica gel using ethyl acetate/petroleum ether (v/v, 1 : 10) as eluent to give 4h as a yellow oil (60.2 mg, 80% yield), Rf = 0.18 (EtOAc/petroleum ether 1 : 10). 1H NMR (CDCl3, 400 MHz), δ: 7.45 (d, J = 6.8 Hz, 1H), 7.35 (t, J = 8.0 Hz, 1H), 7.29 (t, J = 8.0 Hz, 1H), 7.22–7.14 (m, 3H), 6.90 (d, J = 6.8 Hz, 2H), 6.75–6.72 (m, 1H), 5.34 (s, 1H), 4.97 (dd, J1 = 12.4 Hz, J2 = 7.2 Hz, 1H), 4.63 (dd, J1 = 12.4 Hz, J2 = 8.0 Hz, 1H), 4.37–4.24 (m, 2H), 3.76 (s, 3H), 1.34 (t, J = 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3), δ: 194.3, 173.7, 166.1, 159.8, 144.4, 143.6, 139.8, 132.5, 132.2, 131.3, 130.1, 129.6, 121.3, 119.6, 118.5, 113.7, 111.5, 109.5, 65.1, 61.9, 55.3, 35.5, 14.4. IR(KBr) ν: 2932, 2855, 1712, 1628, 1592, 1585, 1452, 1396, 1242, 1109, 1046. HRMS(EI) (m/z): calcd for C23H20O5 (M + H)+: 377.1384; found: 377.1387.

Ethyl-5-(3-chlorophenyl)-6-oxo-5,6-dihydro-2H-indeno[1,2-b]oxepine-4-carboxylate (4i)

In a 5 mL vial, 1,3-dioxo-2,3-dihydro-1H-inden-2-ylium 1a (29.2 mg, 0.2 mmol, 1.0 equiv.), (E)-(4-ethoxy-4-oxobut-2-en-1-yl)dimethylsulfonium bromide 3a (76.5 mg, 1.5 equiv.), Na2CO3 (42 mg, 2 equiv.) and l-proline (2.3 mg, 0.1 equiv.) was added. To this resultant mixture, 3-chlorobenzaldehyde 2i (33.6 mg, 1.2 equiv.) and DCM (2 mL) were added and stirred at room temperature overnight. The reaction was confirmed by TLC. Then the solution was diluted with ethyl acetate and transferred to a round bottom flask. Silica gel was added to the flask and volatiles were evaporated under vacuum. The purification was performed by flash column chromatography on silica gel using ethyl acetate/petroleum ether (v/v, 1 : 10) as eluent to give 4i as a yellow oil (60.8 mg, 80% yield), Rf = 0.22 (EtOAc/petroleum ether 1 : 10). 1H NMR (CDCl3, 400 MHz), δ: 7.46 (d, J = 7.2 Hz, 1H), 7.36 (t, J = 8.0 Hz, 1H), 7.30 (t, 2H), 7.22–7.16 (m, 5H), 5.33 (s, 1H), 4.87 (dd, J1 = 12.4 Hz, J2 = 7.2 Hz, 1H), 4.69–4.64 (m, 1H), 4.38–4.24 (m, 2H), 1.34 (t, J = 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3), δ: 194.2, 173.9, 165.9, 144.0, 143.9, 139.6, 134.5, 132.6, 132.4, 131.2, 130.2, 129.9, 127.3, 127.0, 125.5, 121.4, 118.6, 108.9, 65.1, 62.0, 35.3, 14.3. IR(KBr) ν: 2925, 2855, 1712, 1628, 1585, 1466, 1403, 1235, 1179, 1102, 1032, 983. HRMS(EI) (m/z): calcd for C22H17ClO4 (M + H)+: 381.0888; found: 381.0886.

Ethyl-5-(2-methoxyphenyl)-6-oxo-5,6-dihydro-2H-indeno[1,2-b]oxepine-4-carboxylate (4j)

In a 5 mL vial, 1,3-dioxo-2,3-dihydro-1H-inden-2-ylium 1a (29.2 mg, 0.2 mmol, 1.0 equiv.), (E)-(4-ethoxy-4-oxobut-2-en-1-yl)dimethylsulfonium bromide 3a (76.5 mg, 1.5 equiv.), Na2CO3 (42 mg, 2 equiv.) and l-proline (2.3 mg, 0.1 equiv.) was added. To this resultant mixture, 2-methoxybenzaldehyde 2j (32.6 mg, 1.2 equiv.) and DCM (2 mL) were added and stirred at room temperature overnight. The reaction was confirmed by TLC. Then the solution was diluted with ethyl acetate and transferred to a round bottom flask. Silica gel was added to the flask and volatiles were evaporated under vacuum. The purification was performed by flash column chromatography on silica gel using ethyl acetate/petroleum ether (v/v, 1 : 10) as eluent to give 4j as a yellow solid (45.9 mg, 61% yield), Rf = 0.19 (EtOAc/petroleum ether 1 : 10). Mp 195 °C; 1H NMR (CDCl3, 400 MHz), δ: 7.45 (d, J = 6.8 Hz, 1H), 7.36 (t, J = 8.0 Hz, 1H), 7.29 (t, J = 8.0 Hz, 1H), 7.26 (d, J = 7.2 Hz, 1H), 7.19 (t, J = 6.8 Hz, 2H), 6.88–6.81 (m, 2H), 6.70 (t, J = 8.0 Hz, 1H), 5.31 (s, 1H), 5.04 (dd, J1 = 12.4 Hz, J2 = 8.0 Hz, 1H), 4.53–4.48 (m, 1H), 4.36–4.27 (m, 2H), 3.73 (s, 3H), 1.36 (t, J = 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3), δ: 193.7, 174.5, 166.9, 156.4, 146.5, 139.8, 132.4, 131.4, 130.3, 130.0, 128.7, 128.2, 128.0, 121.2, 120.2, 118.2, 110.8, 107.8, 64.5, 61.2, 55.0, 32.5, 14.4. IR(KBr) ν: 2932, 2848, 1740, 1691, 1642, 1543, 1515, 1459, 1424, 1102, 1046, 997. HRMS(EI) (m/z): calcd for C23H20O5 (M + H)+: 377.1384; found: 377.1386.

Ethyl-5-(2,3-dimethoxyphenyl)-6-oxo-5,6-dihydro-2H-indeno[1,2-b]oxepine-4-carboxylate (4k)

In a 5 mL vial, 1,3-dioxo-2,3-dihydro-1H-inden-2-ylium 1a (29.2 mg, 0.2 mmol, 1.0 equiv.), (E)-(4-ethoxy-4-oxobut-2-en-1-yl)dimethylsulfonium bromide 3a (76.5 mg, 1.5 equiv.), Na2CO3 (42 mg, 2 equiv.) and l-proline (2.3 mg, 0.1 equiv.) was added. To this resultant mixture, 2,3-dimethoxybenzaldehyde 2k (39.8 mg, 1.2 equiv.) and DCM (2 mL) were added and stirred at room temperature overnight. The reaction was confirmed by TLC. Then the solution was diluted with ethyl acetate and transferred to a round bottom flask. Silica gel was added to the flask and volatiles were evaporated under vacuum. The purification was performed by flash column chromatography on silica gel using ethyl acetate/petroleum ether (v/v, 1 : 5) as eluent to give 4k as a yellow solid (53.6 mg, 66% yield), Rf = 0.15 (EtOAc/petroleum ether 1 : 10). Mp 172 °C; 1H NMR (CDCl3, 400 MHz), δ: 7.46 (d, J = 7.2 Hz, 1H), 7.37 (t, 1H), 7.30 (t, 1H), 7.19 (d, J = 7.2 Hz, 1H), 6.95 (t, 1H), 6.88 (d, J = 7.2 Hz, 1H), 6.82–6.76 (m, 2H), 5.36 (s, 1H), 4.51 (dd, J1 = 12.4 Hz, J2 = 8.0 Hz, 1H), 4.51 (dd, J1 = 12.4 Hz, J2 = 7.6 Hz, 1H), 4.30 (q, J = 7.2 Hz, 2H), 3.83 (s, 3H), 3.79 (s, 3H), 1.35 (t, J = 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3), δ: 193.7, 174.3, 166.4, 153.2, 146.3, 146.2, 139.8, 136.2, 132.4, 131.5, 130.1, 128.0, 123.5, 121.3, 121.1, 118.3, 111.5, 108.3, 64.8, 61.5, 60.3, 55.9, 32.3, 14.4. IR(KBr) ν: 2918, 2814, 1726, 1466, 1396, 1291, 1228, 1116, 1032, 983. HRMS(EI) (m/z): calcd for C24H22O6 (M + H)+: 407.1489; found: 407.1488.

Methyl-5-(2,3-dimethoxyphenyl)-6-oxo-5,6-dihydro-2H-indeno[1,2-b]oxepine-4-carboxylate (4l)

In a 5 mL vial, 1,3-dioxo-2,3-dihydro-1H-inden-2-ylium 1a (29.2 mg, 0.2 mmol, 1.0 equiv.), (E)-(4-methoxy-4-oxobut-2-en-1-yl)dimethylsulfonium bromide 3b (72.3 mg, 1.5 equiv.), Na2CO3 (42 mg, 2 equiv.) and l-proline (2.3 mg, 0.1 equiv.) was added. To this resultant mixture, 2,3-dimethoxybenzaldehyde 2l (39.8, 1.2 equiv.) and DCM (2 mL) were added and stirred at room temperature overnight. The reaction was confirmed by TLC. Then the solution was diluted with ethyl acetate and transferred to a round bottom flask. Silica gel was added to the flask and volatiles were evaporated under vacuum. The purification was performed by flash column chromatography on silica gel using ethyl acetate/petroleum ether (v/v, 1 : 10) as eluent to give 4l as a Yellow solid (52.5 mg, 67% yield), Rf = 0.2 (EtOAc/petroleum ether 1 : 10). Mp 181 °C; 1H NMR (CDCl3, 400 MHz), δ: 7.46 (d, J = 6.8 Hz, 1H), 7.37 (t, 1H), 7.30 (t, 1H), 7.19 (d, J = 7.2 Hz, 1H), 6.95 (t, 1H), 6.88 (d, J = 7.2 Hz, 1H), 6.79 (dd, J1 = 19.2 Hz, J2 = 8.0 Hz, 2H), 5.34 (s, 1H), 5.00 (dd, J1 = 12.4 Hz, J2 = 8.0 Hz, 1H), 4.54–4.49 (m, 1H), 3.84 (s, 3H), 3.83 (s, 3H), 3.79 (s, 3H); 13C NMR (101 MHz, CDCl3), δ: 193.8, 174.4, 166.9, 153.2, 146.2, 145.9, 139.8, 136.1, 132.5, 131.5, 130.1, 128.3, 123.6, 121.3, 121.0, 118.4, 111.6, 108.1, 64.7, 60.3, 55.9, 52.5, 32.3. IR(KBr) ν: 2915, 2808, 1733, 1465, 1387, 1283, 1216, 1109, 1022, 981. HRMS(EI) (m/z): calcd for C23H20O6 (M + H)+: 393.1333; found: 393.1335.

Methyl-6-oxo-5-phenyl-5,6-dihydro-2H-indeno[1,2-b]oxepine-4-carboxylate (4m)

In a 5 mL vial, 1,3-dioxo-2,3-dihydro-1H-inden-2-ylium 1a (29.2 mg, 0.2 mmol, 1.0 equiv.), (E)-(4-methoxy-4-oxobut-2-en-1-yl)dimethylsulfonium bromide 3b (72.3 mg, 1.5 equiv.), Na2CO3 (42 mg, 2 equiv.) and l-proline (2.3 mg, 0.1 equiv.) was added. To this resultant mixture, benzaldehyde 2a (25.4 mg, 1.2 equiv.) and DCM (2 mL) were added and stirred at room temperature overnight. The reaction was confirmed by TLC. Then the solution was diluted with ethyl acetate and transferred to a round bottom flask. Silica gel was added to the flask and volatiles were evaporated under vacuum. The purification was performed by flash column chromatography on silica gel using ethyl acetate/petroleum ether (v/v, 1 : 10) as eluent to give 4m as a yellow oil (59.8 mg, 90% yield), Rf = 0.22 (EtOAc/petroleum ether 1 : 10). 1H NMR (CDCl3, 400 MHz), δ: 7.45 (d, J = 7.2 Hz, 1H), 7.37–7.27 (m, 6H), 7.21–7.15 (m, 3H), 5.37 (s, 1H), 4.91 (dd, J1 = 12.4 Hz, J2 = 7.6 Hz, 1H), 4.63 (dd, J1 = 12.4 Hz, J2 = 7.6 Hz, 1H), 3.84 (s, 3H); 13C NMR (101 MHz, CDCl3), δ: 194.3, 173.6, 166.6, 144.2, 141.7, 139.7, 132.5, 132.4, 131.2, 130.0, 128.6, 127.1, 126.7, 121.2, 118.4, 109.5, 65.1, 52.8, 35.5. IR(KBr) ν: 2925, 2848, 1719, 1628, 1459, 1403, 1242, 1102, 1039, 976. HRMS(EI) (m/z): calcd for C21H16O4 (M + H)+: 333.1121; found: 323.1124.

Methyl-5-(4-methoxyphenyl)-6-oxo-5,6-dihydro-2H-indeno[1,2-b]oxepine-4-carboxylate (4n)

In a 5 mL vial, 1,3-dioxo-2,3-dihydro-1H-inden-2-ylium 1a (29.2 mg, 0.2 mmol, 1.0 equiv.), (E)-(4-methoxy-4-oxobut-2-en-1-yl)dimethylsulfonium bromide 3b (72.3 mg, 1.5 equiv.), Na2CO3 (42 mg, 2 equiv.) and l-proline (2.3 mg, 0.1 equiv.) was added. To this resultant mixture, 4-methoxybenzaldehyde 2g (32.6 mg, 1.2 equiv.) and DCM (2 mL) were added and stirred at room temperature overnight. The reaction was confirmed by TLC. Then the solution was diluted with ethyl acetate and transferred to a round bottom flask. Silica gel was added to the flask and volatiles were evaporated under vacuum. The purification was performed by flash column chromatography on silica gel using ethyl acetate/petroleum ether (v/v, 1 : 10) as eluent to give 4n as a yellow solid (60.1 mg, 83% yield), Rf = 0.18 (EtOAc/petroleum ether 1 : 10). Mp 112 °C; 1H NMR (CDCl3, 400 MHz), δ: 7.44 (d, J = 7.0 Hz, 1H), 7.35 (t, 1H), 7.29 (t, 1H), 7.23 (d, 2H), 7.20–7.11 (m, 2H), 6.81 (d, J = 8.8 Hz, 1H), 5.30 (s, 1H); 13C NMR (101 MHz, CDCl3), δ: 194.4, 173.5, 166.7, 158.4, 144.4, 139.8, 133.9, 132.5, 132.3, 131.3, 130.1, 128.2, 121.3, 118.5, 114.0, 109.9, 65.2, 55.4, 52.8, 35.0. IR(KBr) ν: 2981, 2925, 1712, 1628, 1508, 1459, 1403, 1242, 1186, 1095, 1053. HRMS(EI) (m/z): calcd for C22H18O5 (M + H)+: 363.1227; found: 363.1225.

Ethyl-6-oxo-5-(2,3,4-trimethoxyphenyl)-5,6-dihydro-2H-indeno[1,2-b]oxepine-4-carboxylate (4o)

In a 5 mL vial, 1,3-dioxo-2,3-dihydro-1H-inden-2-ylium 1a (29.2 mg, 0.2 mmol, 1.0 equiv.), (E)-(4-ethoxy-4-oxobut-2-en-1-yl)dimethylsulfonium bromide 3a (76.5 mg, 1.5 equiv.), Na2CO3 (42 mg, 2 equiv.) and l-proline (2.3 mg, 0.1 equiv.) was added. To this resultant mixture, 2,3,4-trimethoxybenzaldehyde 2o (47 mg, 1.2 equiv.) and DCM (2 mL) were added and stirred at room temperature overnight. The reaction was confirmed by TLC. Then the solution was diluted with ethyl acetate and transferred to a round bottom flask. Silica gel was added to the flask and volatiles were evaporated under vacuum. The purification was performed by flash column chromatography on silica gel using ethyl acetate/petroleum ether (v/v, 1 : 5) as eluent to give 4o as a Yellow solid (57.6 mg, 66% yield), Rf = 0.11 (EtOAc/petroleum ether 1 : 10). Mp 155 °C; 1H NMR (CDCl3, 400 MHz), δ: 7.44 (d, J = 7.2 Hz, 1H), 7.36 (t, 1H), 7.30 (t, 1H), 7.18 (d, J = 7.2 Hz, 1H), 6.90 (d, J = 8.4 Hz, 1H), 6.79 (t, 1H), 6.52 (d, J = 8.4 Hz, 1H), 5.25 (s, 1H), 4.56–4.51 (m, 1H), 4.33–4.27 (m, 1H), 4.30 (q, 2H), 3.82 (s, 3H), 3.81 (s, 3H), 3.79 (s, 3H), 1.35 (t, J = 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3), δ: 193.8, 174.3, 166.4, 153.1, 151.0, 146.3, 142.5, 139.8, 132.4, 131.4, 130.0, 128.2, 128.1, 123.1, 121.2, 118.3, 108.3, 106.1, 64.7, 61.4, 60.8, 60.4, 56.0, 32.0, 14.4. IR(KBr) ν: 2925, 2855, 1726, 1628, 1466, 1396, 1249, 1109, 1039, 983. HRMS(EI) (m/z): calcd for C25H24O7 (M + H)+: 437.1595; found: 437.1594.

Ethyl-5-(5-methylfuran-2-yl)-6-oxo-5,6-dihydro-2H-indeno[1,2-b]oxepine-4-carboxylate (4p)

In a 5 mL vial, 1,3-dioxo-2,3-dihydro-1H-inden-2-ylium 1a (29.2 mg, 0.2 mmol, 1.0 equiv.), (E)-(4-ethoxy-4-oxobut-2-en-1-yl)dimethylsulfonium bromide 3a (76.5 mg, 1.5 equiv.), Na2CO3 (42 mg, 2 equiv.) and l-proline (2.3 mg, 0.1 equiv.) was added. To this resultant mixture, 5-methylfuran-2-carbaldehyde 2p (26.4 mg, 1.2 equiv.) and DCM (2 mL) were added and stirred at room temperature overnight. The reaction was confirmed by TLC. Then the solution was diluted with ethyl acetate and transferred to a round bottom flask. Silica gel was added to the flask and volatiles were evaporated under vacuum. The purification was performed by flash column chromatography on silica gel using ethyl acetate/petroleum ether (v/v, 1 : 10) as eluent to give 4p as a yellow oil (44.8 mg, 64% yield), Rf = 0.23 (EtOAc/petroleum ether 1 : 10). 1H NMR (CDCl3, 400 MHz), δ: 7.43 (d, J = 7.2 Hz, 1H), 7.35 (t, J = 8.0 Hz, 1H), 7.28 (t, J = 8.0 Hz, 1H), 7.19 (t, 2H), 6.05 (d, J = 2.8 Hz, 1H), 5.84 (d, J = 2.0 Hz, 1H), 5.47 (dd, J1 = 12.4 Hz, J2 = 6.8 Hz, 1H), 5.28 (s, 1H), 4.75 (dd, J1 = 12.4 Hz, J2 = 8.0 Hz, 1H), 4.35–4.21 (m, 2H), 2.22 (s, 3H), 1.33 (t, J = 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3), δ: 193.8, 173.5, 165.5, 151.8, 151.4, 141.6, 139.9, 133.1, 132.5, 131.3, 130.0, 121.3, 118.5, 107.6, 107.5, 106.4, 65.4, 61.7, 31.3, 14.3, 13.8. IR(KBr) ν: 2925, 2848, 1719, 1635, 1585, 1459, 1403, 1242, 1109. HRMS(EI) (m/z): calcd for C21H18O5 (M + H)+: 351.1227; found: 351.1225.

Ethyl-5-(furan-2-yl)-6-oxo-5,6-dihydro-2H-indeno[1,2-b]oxepine-4-carboxylate (4q)

In a 5 mL vial, 1,3-dioxo-2,3-dihydro-1H-inden-2-ylium 1a (29.2 mg, 0.2 mmol, 1.0 equiv.), (E)-(4-ethoxy-4-oxobut-2-en-1-yl)dimethylsulfonium bromide 3a (76.5 mg, 1.5 equiv.), Na2CO3 (42 mg, 2 equiv.) and l-proline (2.3 mg, 0.1 equiv.) was added. To this resultant mixture, furan-2-carbaldehyde 2q (23.4 mg, 1.2 equiv.) and DCM (2 mL) were added and stirred at room temperature overnight. The reaction was confirmed by TLC. Then the solution was diluted with ethyl acetate and transferred to a round bottom flask. Silica gel was added to the flask and volatiles were evaporated under vacuum. The purification was performed by flash column chromatography on silica gel using ethyl acetate/petroleum ether (v/v, 1 : 10) as eluent to give 4q as a yellow oil (40.3 mg, 60% yield), Rf = 0.21 (EtOAc/petroleum ether 1 : 10). 1H NMR (CDCl3, 400 MHz), δ: 7.43 (d, J = 7.2 Hz, 1H), 7.35 (t, 1H), 7.29 (d, 2H), 7.19 (dd, J1 = 8.0 Hz, J2 = 12.0 Hz, 2H), 6.27 (dd, J1 = 3.2 Hz, J2 = 2.0 Hz, 1H), 6.18 (d, J = 3.2 Hz, 1H), 5.41–5.36 (m, 1H), 5.33 (s, 1H), 4.75 (dd, J1 = 12.4 Hz, J2 = 8.0 Hz, 1H), 4.34–4.23 (m, 2H), 1.32 (t, J = 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3), δ: 193.8, 173.7, 165.4, 153.4, 142.1, 141.4, 139.8, 133.3, 132.5, 131.3, 130.1, 121.3, 118.6, 110.5, 107.3, 106.8, 65.3, 61.8, 31.3, 14.3. IR(KBr) ν: 2918, 2848, 1712, 1635, 1543, 1508, 1459, 1403, 1242, 1109, 1046, 1004. HRMS(EI) (m/z): calcd for C25H21NO4 (M + H)+: 337.1071; found: 337.1076.

Ethyl-6-oxo-5-(thiophen-2-yl)-5,6-dihydro-2H-indeno[1,2-b]oxepine-4-carboxylate (4r)

In a 5 mL vial, 1,3-dioxo-2,3-dihydro-1H-inden-2-ylium 1a (29.2 mg, 0.2 mmol, 1.0 equiv.), (E)-(4-ethoxy-4-oxobut-2-en-1-yl)dimethylsulfonium bromide 3a (76.5 mg, 1.5 equiv.), Na2CO3 (42 mg, 2 equiv.) and l-proline (2.3 mg, 0.1 equiv.) was added. To this resultant mixture, thiophene-2-carbaldehyde 2r (26.9 mg, 1.2 equiv.) and DCM (2 mL) were added and stirred at room temperature overnight. The reaction was confirmed by TLC. Then the solution was diluted with ethyl acetate and transferred to a round bottom flask. Silica gel was added to the flask and volatiles were evaporated under vacuum. The purification was performed by flash column chromatography on silica gel using ethyl acetate/petroleum ether (v/v, 1 : 10) as eluent to give 4r as a yellow oil (50 mg, 71% yield), Rf = 0.24 (EtOAc/petroleum ether 1 : 10). 1H NMR (CDCl3, 400 MHz), δ: 7.44 (d, J = 7.2 Hz, 1H), 7.35 (t, J = 8.0 Hz, 1H), 7.29 (t, 1H), 7.19–7.13 (m, 3H), 6.91–6.88 (m, 2H), 5.46 (s, 1H), 5.19–5.15 (m, 1H) 4.71 (dd, J1 = 12.8 Hz, J2 = 8.0 Hz, 1H), 4.37–4.24 (m, 2H), 1.34 (t, J = 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3), δ: 193.8, 173.5, 165.5, 145.5, 143.6, 139.6, 132.7, 132.6, 131.1, 130.2, 126.8, 124.7, 124.4, 121.4, 118.7, 109.6, 65.2, 61.9, 32.4, 14.3. IR(KBr) ν: 2925, 2855, 1705, 1628, 1585, 1466, 1396, 1242, 1109, 1046. HRMS(EI) (m/z): calcd for C20H16O4S (M + H)+: 353.0842; found: 353.0845.

Ethyl-6-oxo-5-(pyridin-3-yl)-5,6-dihydro-2H-indeno[1,2-b]oxepine-4-carboxylate (4s)

In a 5 mL vial, 1,3-dioxo-2,3-dihydro-1H-inden-2-ylium 1a (29.2 mg, 0.2 mmol, 1.0 equiv.), (E)-(4-ethoxy-4-oxobut-2-en-1-yl)dimethylsulfonium bromide 3a (76.5 mg, 1.5 equiv.), Na2CO3 (42 mg, 2 equiv.) and l-proline (2.3 mg, 0.1 equiv.) was added. To this resultant mixture, nicotinaldehyde 2s (25.7 mg, 1.2 equiv.) and DCM (2 mL) were added and stirred at room temperature overnight. The reaction was confirmed by TLC. Then the solution was diluted with ethyl acetate and transferred to a round bottom flask. Silica gel was added to the flask and volatiles were evaporated under vacuum. The purification was performed by flash column chromatography on silica gel using ethyl acetate/petroleum ether (v/v, 1 : 10) as eluent to give 4s as a brown oil (39.6 mg, 57% yield), Rf = 0.18 (EtOAc/petroleum ether 1 : 10). 1H NMR (CDCl3, 400 MHz), δ: 8.56 (s, 1H), 8.44 (d, 1H), 7.67 (d, J = 8.0 Hz, 1H), 7.44 (d, J = 7.2 Hz, 1H), 7.36 (t, 1H), 7.29 (t, J = 7.2 Hz, 1H), 7.22–7.17 (m, 3H), 5.35 (s, 1H), 4.84 (dd, J1 = 12.4 Hz, J2 = 7.2 Hz, 1H), 4.73–4.68 (m, 1H), 4.34–4.25 (m, 2H), 1.33 (t, J = 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3), δ: 194.2, 174.0, 165.8, 148.4, 148.1, 143.3, 139.5, 137.5, 135.2, 132.7, 132.7, 131.1, 130.3, 129.6, 123.5, 121.4, 118.7, 108.4, 65.2, 62.1, 33.9, 14.3. IR(KBr) ν: 2974, 2925, 1705, 1621, 1585, 1550, 1459, 1410, 1256, 1116, 1046. HRMS(EI) (m/z): calcd for C21H17NO4 (M + H)+: 348.1230; found: 348.1227.

Ethyl-5-(1H-indol-3-yl)-6-oxo-5,6-dihydro-2H-indeno[1,2-b]oxepine-4-carboxylate (4t)

In a 5 mL vial, 1,3-dioxo-2,3-dihydro-1H-inden-2-ylium 1a (29.2 mg, 0.2 mmol, 1.0 equiv.), (E)-(4-ethoxy-4-oxobut-2-en-1-yl)dimethylsulfonium bromide 3a (76.5 mg, 1.5 equiv.), Na2CO3 (42 mg, 2 equiv.) and l-proline (2.3 mg, 0.1 equiv.) was added. To this resultant mixture, 1H-indole-3-carbaldehyde 2t (34.8 mg, 1.2 equiv.) and DCM (2 mL) were added and stirred at room temperature overnight. The reaction was confirmed by TLC. Then the solution was diluted with ethyl acetate and transferred to a round bottom flask. Silica gel was added to the flask and volatiles were evaporated under vacuum. The purification was performed by flash column chromatography on silica gel using ethyl acetate/petroleum ether (v/v, 1 : 5) as eluent to give 4t as a yellow solid (29.3 mg, 38% yield), Rf = 0.15 (EtOAc/petroleum ether 1 : 10). Mp 183 °C; 1H NMR (CDCl3, 400 MHz), δ: 7.69 (d, J = 8.0 Hz, 1H), 7.46 (d, J = 8.0 Hz, 1H), 7.36 (t, 1H), 7.29 (d, J = 8.0 Hz, 2H), 4.84 (dd, J1 = 12.4 Hz, J2 = 7.2 Hz, 1H), 7.12–7.05 (m, 2H), 6.98 (m, 1H), 5.54 (t, J = 1.2 Hz, 1H), 5.40–5.35 (m, 1H), 4.61 (dd, J1 = 12.4 Hz, J2 = 8.0 Hz, 1H), 4.39–4.31 (m, 2H), 1.36 (t, J = 6.8 Hz, 3H); 13C NMR (101 MHz, CDCl3), δ: 194.0, 173.6, 166.1, 144.1, 139.8, 137.0, 132.4, 132.1, 131.3, 129.9, 125.8, 122.9, 122.3, 121.2, 120.1, 119.7, 118.3, 117.4, 111.2, 109.8, 64.5, 61.8, 28.5, 14.3. IR(KBr) ν: 2939, 1719, 1635, 1200, 1144. HRMS(EI) (m/z): calcd for C25H21NO4 (M + H)+: 86.1543; found: 386.1541.

Ethyl-5-(1-methyl-1H-indol-3-yl)-6-oxo-5,6-dihydro-2H-indeno[1,2-b]oxepine-4-carboxylate (4u)

In a 5 mL vial, 1,3-dioxo-2,3-dihydro-1H-inden-2-ylium 1a (29.2 mg, 0.2 mmol, 1.0 equiv.), (E)-(4-ethoxy-4-oxobut-2-en-1-yl)dimethylsulfonium bromide 3a (76.5 mg, 1.5 equiv.), Na2CO3 (42 mg, 2 equiv.) and l-proline (2.3 mg, 0.1 equiv.) was added. To this resultant mixture, 1-methyl-1H-indole-3-carbaldehyde 2u (38.1 mg, 1.2 equiv.) and DCM (2 mL) were added and stirred at room temperature overnight. The reaction was confirmed by TLC. Then the solution was diluted with ethyl acetate and transferred to a round bottom flask. Silica gel was added to the flask and volatiles were evaporated under vacuum. The purification was performed by flash column chromatography on silica gel using ethyl acetate/petroleum ether (v/v, 1 : 5) as eluent to give 4u as a yellow oil (55.9 mg, 70% yield), Rf = 0.12 (EtOAc/petroleum ether 1 : 10). 1H NMR (CDCl3, 400 MHz), δ: 7.67 (d, J = 8.0 Hz, 1H), 7.46 (d, J = 7.2 Hz, 1H), 7.37 (t, J = 8.0 Hz, 1H), 7.30 (t, J = 8.0 Hz, 1H), 7.24–7.18 (m, 3H), 7.12–7.05 (m, 2H), 6.87 (s, 1H), 5.53 (s, 1H), 5.44–5.39 (m, 1H), 4.65–4.60 (m, 1H), 4.39–4.33 (m, 2H), 3.70 (s, 3H), 1.37 (t, J = 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3), δ: 194.1, 173.6, 166.2, 144.4, 139.9, 137.8, 132.5, 132.1, 131.4, 130.0, 127.7, 126.3, 122.0, 121.3, 120.4, 119.3, 118.3, 115.8, 110.1, 109.3, 64.7, 61.8, 32.9, 29.8, 28.6, 14.4. IR(KBr) ν: 2925, 2855, 1719, 1628, 1585, 1473, 1403, 1235, 1109, 1039, 983. HRMS(EI) (m/z): calcd for C25H21NO4 (M + H)+: 400.1543; found: 400.1544.

Ethyl-(E)-3-(2,2-dicyano-3-phenylcyclopropyl)acrylate (6a)

A mixture of malononitrile 5a (13.2 mg, 1 equiv.), (E)-(4-ethoxy-4-oxobut-2-en-1-yl)dimethylsulfonium bromide 3a (76.5 mg, 1.5 equiv.), Na2CO3 (42 mg, 2 equiv.), l-proline (2.3 mg, 0.1 equiv.) and benzaldehyde 2a (25.4 mg, 1.2 equiv.) in DCM. The reaction mixture was stirred at 0 °C overnight. The reaction mixture was concentrated in vacuo. The residue was purified by column chromatography (EA : PE, 1 : 10) to afford compound 6a as a brown oil (44.2 mg, 83% yield), Rf = 0.17 (EtOAc/petroleum ether 1 : 10). 1H NMR (CDCl3, 400 MHz), δ: 7.43 (m, 3H), 7.32 (m, 2H), 6.43–6.34 (m, 2H), 4.23–4.18 (m, 2H), 3.57 (d, J = 9.6 Hz, 1H), 3.15–3.10 (m, 1H), 1.28 (t, J = 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3), δ: 164.4, 136.1, 129.9, 129.6, 129.6, 129.1, 128.2, 114.8, 111.1, 61.2, 38.5, 36.4, 14.3, 12.3. IR(KBr) ν: 2927.97, 2253.41, 1721.18, 1646.23, 1271.47, 1162.45, 1039.80, 971.66, 740.00, 692.30. HRMS(EI) (m/z): calcd for C16H14N2O2 (M + H)+: 267.1128; found: 267.1123.

Ethyl-(E)-3-(2,2-dicyano-3-(4-nitrophenyl)cyclopropyl)acrylate (6b)

A mixture of malononitrile 5a (13.2 mg, 1 equiv.), (E)-(4-ethoxy-4-oxobut-2-en-1-yl)dimethylsulfonium bromide 3a (76.5 mg, 1.5 equiv.), Na2CO3 (42 mg, 2 equiv.), l-proline (2.3 mg, 0.1 equiv.) and 4-nitrobenzaldehyde 2b (36.2 mg, 1.2 equiv.) in DCM. The reaction mixture was stirred at 0 °C overnight. The reaction mixture was concentrated in vacuo. The residue was purified by column chromatography (EA : PE, 1 : 5) to afford compound 6b as a yellow oil (46.7 mg, 75% yield), Rf = 0.23 (EtOAc/petroleum ether 1 : 5).1H NMR (CDCl3, 400 MHz), δ: 8.29 (d, 2H), 7.43 (d, 2H), 7.05 (s, 1H), 4.90 (s, 1H), 4.14 (dd, J1 = 7.2 Hz, J2 = 4.0 Hz, 2H), 3.48 (m, 2H), 1.17 (t, J = 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3), δ: 161.7, 148.6, 141.2, 139.4, 136.6, 129.3, 124.6, 115.9, 113.1, 61.8, 59.6, 44.0, 39.8, 14.1. IR(KBr) ν: 2918, 2245, 1719, 1649, 1494, 1466, 1256, 1165, 1032, 976, 751. HRMS(EI) (m/z): calcd for C16H13N3O4 (M + H)+: 312.0979; found: 312.0976.

Ethyl-(E)-3-(2,2-dicyano-3-(4-cyanophenyl)cyclopropyl)acrylate (6c)

A mixture of malononitrile 5a (13.2 mg, 1 equiv.), (E)-(4-ethoxy-4-oxobut-2-en-1-yl)dimethylsulfonium bromide 3a (76.5 mg, 1.5 equiv.), Na2CO3 (42 mg, 2 equiv.), l-proline (2.3 mg, 0.1 equiv.) and 4-formylbenzonitrile 2c (31.4 mg, 1.2 equiv.) in DCM. The reaction mixture was stirred at 0 °C overnight. The reaction mixture was concentrated in vacuo. The residue was purified by column chromatography (EA : PE, 1 : 3) to afford compound 6c as a white solid (40.2 mg, 69% yield), Rf = 0.22 (EtOAc/petroleum ether 1 : 3). Mp 151 °C; 1H NMR (CDCl3, 400 MHz), δ: 7.75 (d, 2H), 7.46 (d, 2H), 6.41 (d, J = 15.2 Hz, 1H), 6.27 (dd, J1 = 15.6 Hz, J2 = 10.0 Hz, 1H), 4.21 (dd, J1 = 14.0 Hz, J2 = 7.2 Hz, 2H), 3.57 (d, J = 10.0 Hz, 1H), 3.20 (t, J = 10.0 Hz, 1H), 1.28 (t, J = 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3), δ: 164.1, 134.8, 133.3, 133.3, 130.8, 130.1, 117.9, 114.0, 113.9, 110.7, 61.4, 37.5, 35.9, 14.3, 12.4. IR(KBr) ν: 2925, 2231, 1733, 1642, 1438, 1284, 1228, 1046. HRMS(EI) (m/z): calcd for C17H13N3O2 (M + H)+: 292.1081; found: 292.1080.

Ethyl-(E)-3-(2,2-dicyano-3-(4-(dimethylamino)phenyl)cyclopropyl)acrylate (6d)

A mixture of malononitrile 5a (13.2 mg, 1 equiv.), (E)-(4-ethoxy-4-oxobut-2-en-1-yl)dimethylsulfonium bromide 3a (76.5 mg, 1.5 equiv.), Na2CO3 (42 mg, 2 equiv.), l-proline (2.3 mg, 0.1 equiv.) and 4-(dimethylamino)benzaldehyde 2d (35.8 mg, 1.2 equiv.) in DCM. The reaction mixture was stirred at 0 °C overnight. The reaction mixture was concentrated in vacuo. The residue was purified by column chromatography (EA : PE, 1 : 5) to afford compound 6d as a brown oil (55 mg, 89% yield), Rf = 0.17 (EtOAc/petroleum ether 1 : 5). 1H NMR (CDCl3, 400 MHz), δ: 7.13 (d, 2H), 6.74–6.67 (m, 3H), 6.30 (d, J = 16.0 Hz, 1H), 4.28–4.22 (m, 2H), 3.27 (d, J = 8.4 Hz, 1H), 3.06 (t, J = 8.8 Hz, 1H), 2.98 (s, 6H), 1.32 (t, J = 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3), δ: 164.7, 151.2, 138.4, 129.1, 128.2, 115.9, 113.3, 112.7, 112.4, 61.2, 41.1, 40.3, 35.5, 14.9, 14.3. IR(KBr) ν: 2925, 2245, 1712, 1614, 1536, 1354, 1277, 1165, 1095, 1039, 964, 822. HRMS(EI) (m/z): calcd for C18H19N3O2 (M + H)+: 310.1550; found: 310.1553.

Ethyl-(E)-3-(2,2-dicyano-3-(2-methoxyphenyl)cyclopropyl)acrylate (6e)

A mixture of malononitrile 5a (13.2 mg, 1 equiv.), (E)-(4-ethoxy-4-oxobut-2-en-1-yl)dimethylsulfonium bromide 3a (76.5 mg, 1.5 equiv.), Na2CO3 (42 mg, 2 equiv.), l-proline (2.3 mg, 0.1 equiv.) and 2-methoxybenzaldehyde 2e (32.6 mg, 1.2 equiv.) in DCM. The reaction mixture was stirred at 0 °C overnight. The reaction mixture was concentrated in vacuo. The residue was purified by column chromatography (EA : PE, 1 : 5) to afford compound 6e as a white solid (44.4 mg, 75% yield), Rf = 0.46 (EtOAc/petroleum ether 1 : 3). Mp 118 °C; 1H NMR (CDCl3, 400 MHz), δ: 7.40 (t, J = 8.0 Hz, 1H), 7.12 (d, J = 7.6 Hz, 1H), 7.01–6.94 (m, 2H), 6.45 (dd, J1 = 15.6 Hz, J2 = 10.0 Hz, 1H), 6.35 (d, J = 15.6 Hz, 1H), 4.24–4.19 (m, 2H), 3.93 (s, 3H), 3.29 (d, J = 9.6 Hz, 1H), 3.11 (t, J = 9.2 Hz, 1H), 1.28 (t, J = 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3), δ: 164.6, 158.7, 137.1, 131.2, 130.3, 128.4, 120.8, 116.9, 115.1, 111.7, 111.3, 61.1, 55.8, 36.2, 35.0, 14.3, 13.1. IR(KBr) ν: 2921, 2245, 1714, 1646, 1503, 1462, 1257, 1162, 1026, 978, 753. HRMS(EI) (m/z): calcd for C17H16N2O3 (M + H)+: 297.1234; found: 297.1229.

Ethyl-(E)-3-(2,2-dicyano-3-(2,3,4-trimethoxyphenyl)cyclopropyl)acrylate (6f)

A mixture of malononitrile 5a (13.2 mg, 1 equiv.), (E)-(4-ethoxy-4-oxobut-2-en-1-yl)dimethylsulfonium bromide 3a (76.5 mg, 1.5 equiv.), Na2CO3 (42 mg, 2 equiv.), l-proline (2.3 mg, 0.1 equiv.) and 2,3,4-trimethoxybenzaldehyde 2o (47 mg, 1.2 equiv.) in DCM. The reaction mixture was stirred at 0 °C overnight. The reaction mixture was concentrated in vacuo. The residue was purified by column chromatography (EA : PE, 1 : 3) to afford compound 6f as a white solid (49.8 mg, 70% yield), Rf = 0.22 (EtOAc/petroleum ether 1 : 3). Mp 115 °C; 1H NMR (CDCl3, 400 MHz), δ: 6.81 (d, J = 8.4 Hz, 1H), 6.61 (d, J = 8.4 Hz, 1H), 6.53–6.46 (m, 1H), 6.34 (d, J = 15.6 Hz, 1H), 4.25–4.19 (m, 2H), 4.08 (s, 3H), 3.87 (s, 3H), 3.86 (s, 3H), 3.29 (d, J = 9.2 Hz, 1H), 3.08 (t, J = 10.0 Hz, 1H), 1.29 (t, J = 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3), δ: 164.6, 155.4, 153.3, 141.9, 137.1, 128.5, 124.7, 115.0, 114.0, 111.8, 106.6, 61.4, 61.1, 61.1, 56.1, 36.2, 35.3, 14.3, 13.0. IR(KBr) ν: 2925, 2848, 2252, 1719, 1656, 1607, 1494, 1466, 1424, 1312, 1263, 1158, 1095, 1039, 976. HRMS(EI) (m/z): calcd for C19H20N2O5 (M + H)+: 357.1445; found: 357.1447.

Ethyl-(E)-3-(2,2-dicyano-3-(pyridin-3-yl)cyclopropyl)acrylate (6g)

A mixture of malononitrile 5a (13.2 mg, 1 equiv.), (E)-(4-ethoxy-4-oxobut-2-en-1-yl)dimethylsulfonium bromide 3a (76.5 mg, 1.5 equiv.), Na2CO3 (42 mg, 2 equiv.), l-proline (2.3 mg, 0.1 equiv.) and nicotinaldehyde 2s (25.7 mg, 1.2 equiv.) (25.4 mg, 1.2 equiv.) in DCM. The reaction mixture was stirred at 0 °C overnight. The reaction mixture was concentrated in vacuo. The residue was purified by column chromatography (EA : PE, 1 : 5) to afford compound 6g as a yellow oil (35.8 mg, 67% yield), Rf = 0.24 (EtOAc/petroleum ether 1 : 5). 1H NMR (CDCl3, 400 MHz), δ: 8.66 (d, J = 3.6 Hz, 1H), 8.52 (s, 1H), 7.56 (dt, J1 = 8.0 Hz, J2 = 2.0 Hz, 1H), 7.37 (dd, J1 = 7.6 Hz, J2 = 4.8 Hz, 1H), 7.02 (dd, J1 = 4.0 Hz, J2 = 2.4 Hz, 1H), 4.81 (s, 1H), 4.19–4.08 (m, 2H), 3.51–3.39 (m, 2H), 1.16 (t, J = 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3), δ: 161.8, 150.9, 149.2, 139.0, 136.6, 135.8, 130.1, 124.1, 116.1, 113.3, 61.7, 57.8, 43.8, 40.0, 14.1. IR(KBr) ν: 1712, 1642, 1249, 1102, 1025, 709. HRMS(EI) (m/z): calcd for C15H13N3O2 (M + H)+: 268.1081; found: 268.1085.

Ethyl-(E)-3-(2,2-dicyano-3-(5-methylfuran-2-yl)cyclopropyl)acrylate (6h)

A mixture of malononitrile 5a (13.2 mg, 1 equiv.), (E)-(4-ethoxy-4-oxobut-2-en-1-yl)dimethylsulfonium bromide 3a (76.5 mg, 1.5 equiv.), Na2CO3 (42 mg, 2 equiv.), l-proline (2.3 mg, 0.1 equiv.) and 5-methylfuran-2-carbaldehyde 2p (26.4 mg, 1.2 equiv.) in DCM. The reaction mixture was stirred at 0 °C overnight. The reaction mixture was concentrated in vacuo. The residue was purified by column chromatography (EA : PE, 1 : 10) to afford compound 6h as a brown oil (36.2 mg, 67% yield), Rf = 0.45 (EtOAc/petroleum ether 1 : 5). 1H NMR (CDCl3, 400 MHz), δ: 6.81 (dd, J1 = 15.6, J2 = 10.0 Hz, 1H), 6.33 (d, 2H), 5.99 (s, 1H), 4.27–4.21 (m, 2H), 3.43 (d, J = 9.6 Hz, 1H), 3.05 (t, J = 10.0 Hz, 1H), 2.30 (s, 3H), 1.31 (t, J = 6.8 Hz, 3H); 13C NMR (101 MHz, CDCl3), δ: 164.5, 154.6, 140.5, 135.7, 129.5, 114.2, 113.6, 110.9, 107.2, 61.2, 35.4, 32.9, 14.3, 13.7, 12.7. IR(KBr) ν: 2921, 2362, 1714, 1653, 1278, 1039, 978, 571. HRMS(EI) (m/z): calcd for C15H14N2O3 (M + H)+: 271.1077; found: 277.1072.

Ethyl-(E)-3-(2,2-dicyano-3-(furan-2-yl)cyclopropyl)acrylate (6i)

A mixture of malononitrile 5a (13.2 mg, 1 equiv.), (E)-(4-ethoxy-4-oxobut-2-en-1-yl)dimethylsulfonium bromide 3a (76.5 mg, 1.5 equiv.), Na2CO3 (42 mg, 2 equiv.), l-proline (2.3 mg, 0.1 equiv.) and furan-2-carbaldehyde 2q (23.4 mg, 1.2 equiv.) in DCM. The reaction mixture was stirred at 0 °C overnight. The reaction mixture was concentrated in vacuo. The residue was purified by column chromatography (EA : PE, 1 : 10) to afford compound 6i as a yellow oil (42 mg, 82% yield), Rf = 0.5 (EtOAc/petroleum ether 1 : 5). 1H NMR (CDCl3, 400 MHz), δ: 7.46 (d, 1H), 6.69 (dd, J1 = 15.6 Hz, J2 = 10.0 Hz, 1H), 6.48–6.39 (m, 2H), 6.32 (t, J = 17.2 Hz, 1H), 4.26–4.21 (m, 2H), 2.78 (d, J = 10.0 Hz, 1H), 1.81 (s, 1H), 1.30 (t, J = 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3), δ: 164.4, 146.5, 144.1, 143.7, 136.5, 128.9, 111.3, 111.2, 110.8, 61.1, 42.5, 37.6, 23.0, 14.2. IR(KBr) ν: 2918, 2245, 1712, 1656, 1452, 1270, 1039, 976, 744, 667. HRMS(EI) (m/z): calcd for C14H12N2O3 (M + H)+: 257.0921; found: 257.0923.

Ethyl-(E)-3-(2,2-dicyano-3-(thiophen-2-yl)cyclopropyl)acrylate (6j)

A mixture of malononitrile 5a (13.2 mg, 1 equiv.), (E)-(4-ethoxy-4-oxobut-2-en-1-yl)dimethylsulfonium bromide 3a (76.5 mg, 1.5 equiv.), Na2CO3 (42 mg, 2 equiv.), l-proline (2.3 mg, 0.1 equiv.) and thiophene-2-carbaldehyde 2s (26.9 mg, 1.2 equiv.) in DCM. The reaction mixture was stirred at 0 °C overnight. The reaction mixture was concentrated in vacuo. The residue was purified by column chromatography (EA : PE, 1 : 10) to afford compound 6j as a yellow oil (42.4 mg, 78% yield), Rf = 0.24 (EtOAc/petroleum ether 1 : 10). 1H NMR (CDCl3, 400 MHz), δ: 7.39 (d, J = 5.2 Hz, 1H), 7.16–7.14 (m, 1H), 7.07–7.04 (m, 1H), 6.67–6.61 (m, 1H), 6.37 (d, J = 15.6 Hz, 1H), 4.23 (q, 2H), 3.59 (d, J = 9.6 Hz, 1H), 3.14 (t, 1H), 1.30 (t, J = 6.8 Hz, 3H); 13C NMR (101 MHz, CDCl3), δ: 164.4, 135.3, 129.9, 129.8, 129.7, 128.1, 127.8, 114.2, 110.9, 61.3, 36.8, 34.2, 14.3, 13.9. IR(KBr) ν: 2918, 2245, 1719, 1649, 1459, 1375, 1319, 1277, 1172, 1102, 1039, 969, 857, 702. HRMS(EI) (m/z): calcd for C14H12N2O2S (M + H)+: 273.0692; found: 273.0694.

Ethyl-(E)-3-(2,2-dicyano-3-(1-methyl-1H-indol-2-yl)cyclopropyl)acrylate (6k)

A mixture of malononitrile 5a (13.2 mg, 1 equiv.), (E)-(4-ethoxy-4-oxobut-2-en-1-yl)dimethylsulfonium bromide 3a (76.5 mg, 1.5 equiv.), Na2CO3 (42 mg, 2 equiv.), l-proline (2.3 mg, 0.1 equiv.) and 1-methyl-1H-indole-3-carbaldehyde 2u (38.1 mg, 1.2 equiv.) in DCM. The reaction mixture was stirred at 0 °C overnight. The reaction mixture was concentrated in vacuo. The residue was purified by column chromatography (EA : PE, 1 : 3) to afford compound 6k as a brown yellow (49.8 mg, 78% yield), Rf = 0.21 (EtOAc/petroleum ether 1 : 3). Mp 113 °C; 1H NMR (CDCl3, 400 MHz), δ: 7.62 (d, J = 8.0 Hz, 1H), 7.37–7.31 (m, 2H), 7.25–7.22 (m, 1H), 7.06 (s, 1H), 6.79 (dd, J1 = 15.6 Hz, J2 = 8.8 Hz, 1H), 6.35 (d, J = 16.0 Hz, 1H), 4.30–4.24 (m, 2H), 3.81 (s, 3H), 3.45 (d, J = 8.4 Hz, 1H), 3.02 (t, J = 8.8 Hz, 1H), 1.33 (t, J = 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3), δ: 164.7, 138.3, 137.2, 128.4, 127.5, 123.2, 120.7, 118.2, 113.2, 112.9, 110.2, 104.3, 61.3, 36.5, 33.9, 33.3, 14.9, 14.3. IR(KBr) ν: 2918, 1719, 1656, 1466, 1375, 1270, 1214, 1039, 976, 737. HRMS(EI) (m/z): calcd for C19H17N3O2 (M + H)+: 320.1394; found: 320.1389.

Ethyl-(E)-3-(2,2-dicyano-3-phenethylcyclopropyl)acrylate (6l)

A mixture of malononitrile 5a (13.2 mg, 1 equiv.), (E)-(4-ethoxy-4-oxobut-2-en-1-yl)dimethylsulfonium bromide 3a (76.5 mg, 1.5 equiv.), Na2CO3 (42 mg, 2 equiv.), l-proline (2.3 mg, 0.1 equiv.) and 3-phenylpropanal 2v (32.2 mg, 1.2 equiv.) in DCM. The reaction mixture was stirred at 0 °C overnight. The reaction mixture was concentrated in vacuo. The residue was purified by column chromatography (EA : PE, 1 : 10) to afford compound 6l as a brown oil (33.5 mg, 57% yield), Rf = 0.24 (EtOAc/petroleum ether 1 : 10). 1H NMR (CDCl3, 400 MHz), δ: 7.32 (t, 2H), 7.24–7.18 (m, 3H), 6.48 (dd, J1 = 15.6 Hz, J2 = 10.0 Hz, 1H), 6.18 (d, J = 15.2 Hz, 1H), 4.26–4.20 (m, 2H), 2.91–2.78 (m, 2H), 2.73 (t, J = 10.0 Hz, 1H), 2.24–2.18 (m, 1H), 2.13–1.94 (m, 2H), 1.31 (t, J = 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3), δ: 164.5, 139.2, 134.7, 129.5, 129.0, 128.7, 128.7, 128.6, 127.0, 114.6, 111.4, 61.2, 35.6, 35.1, 34.1, 27.4, 14.3, 11.1. IR(KBr) ν: 2924, 1634.18, 1454.10, 1202.00, 1036.32, 748.19, 697. HRMS(EI) (m/z): calcd for C18H18N2O2 (M + H)+: 295.1441; found: 295.1445.

Methyl-(E)-3-(2,2-dicyano-3-phenylcyclopropyl)acrylate (6m)

A mixture of malononitrile 5a (13.2 mg, 1 equiv.), (E)-(4-methoxy-4-oxobut-2-en-1-yl)dimethylsulfonium bromide 3b (72.3 mg, 1.5 equiv.), Na2CO3 (42 mg, 2 equiv.), l-proline (2.3 mg, 0.1 equiv.) and benzaldehyde 2a (25.4 mg, 1.2 equiv.) in DCM. The reaction mixture was stirred at 0 °C overnight. The reaction mixture was concentrated in vacuo. The residue was purified by column chromatography (EA : PE, 1 : 5) to afford compound 6m as a white solid (42.3 mg, 84% yield), Rf = 0.16 (EtOAc/petroleum ether 1 : 10). Mp 122 °C; 1H NMR (CDCl3, 400 MHz), δ: 7.37 (s, 3H), 7.21–7.15 (m, 1H), 6.33–6.32 (m, 2H), 3.69 (d, J = 3.6 Hz, 3H), 3.52 (d, J = 9.6 Hz, 1H), 3.10–3.05 (m, 1H). 13C NMR (101 MHz, CDCl3), δ: 164.4, 135.3, 130.0, 129.7, 129.7, 128.1, 127.8, 114.2, 110.9, 61.3, 36.8, 34.2, 14.3, 13.9. IR(KBr) ν: 2918, 2848, 2252, 1726, 1656, 1438, 1270, 1039, 737, 695. HRMS(EI) (m/z): calcd for C15H12N2O2 (M + H)+: 253.0972; found: 253.0966.

Methyl-(E)-3-(2,2-dicyano-3-(4-(dimethylamino)phenyl)cyclopropyl)acrylate (6n)

A mixture of malononitrile 5a (13.2 mg, 1 equiv.), (E)-(4-methoxy-4-oxobut-2-en-1-yl)dimethylsulfonium bromide 3b (72.3 mg, 1.5 equiv.), Na2CO3 (42 mg, 2 equiv.), l-proline (2.3 mg, 0.1 equiv.) and 4-(dimethylamino)benzaldehyde 2f (35.8 mg, 1.2 equiv.) in DCM. The reaction mixture was stirred at 0 °C overnight. The reaction mixture was concentrated in vacuo. The residue was purified by column chromatography (EA : PE, 1 : 5) to afford compound 6n as a brown oil (52.5 mg, 89% yield), Rf = 0.34 (EtOAc/petroleum ether 1 : 5). 1H NMR (CDCl3, 400 MHz), δ: 7.13 (d, J = 8.8 Hz, 2H), 6.75–6.68 (m, 3H), 6.31 (d, J = 15.2 Hz, 1H), 3.79 (s, 3H), 3.27 (d, J = 8.4 Hz, 1H), 3.06 (t, J = 8.8 Hz, 1H), 2.98 (s, 6H); 13C NMR (101 MHz, CDCl3), δ: 165.1, 151.2, 138.8, 129.1, 127.7, 115.9, 113.3, 112.6, 112.4, 52.3, 41.2, 40.3, 35.5, 14.9. IR(KBr) ν: 2918, 1726, 1529, 1277, 1116, 1046, 983. HRMS(EI) (m/z): calcd for C17H17N3O2 (M + H)+: 296.1394; found: 296.1396.

Methyl-1-cyano-2-((E)-3-methoxy-3-oxoprop-1-en-1-yl)-3-phenylcyclopropane-1-carboxylate (6o)

A mixture of methyl 2-cyanoacetate 5b (19.8 mg, 1 equiv.), (E)-(4-methoxy-4-oxobut-2-en-1-yl)dimethylsulfonium bromide 3b (72.3 mg, 1.5 equiv.), Na2CO3 (42 mg, 2 equiv.), l-proline (2.3 mg, 0.1 equiv.) and benzaldehyde 2a (25.4 mg, 1.2 equiv.) in DCM. The reaction mixture was stirred at 0 °C overnight. The reaction mixture was concentrated in vacuo. The residue was purified by column chromatography (EA : PE, 1 : 5) to afford compound 6o as a white oil (42.2 mg, 74% yield), Rf = 0.15 (EtOAc/petroleum ether 1 : 10). 1H NMR (CDCl3, 400 MHz), δ: 7.42–7.36 (m, 3H), 7.29 (d, 2H), 6.95 (dd, J1 = 15.6 Hz, J2 = 9.6 Hz, 1H), 6.25 (d, J = 15.6 Hz, 1H), 3.88 (s, 3H), 3.76 (s, 3H), 3.53 (d, J = 8.4 Hz, 1H), 3.08 (t, 1H); 13C NMR (101 MHz, CDCl3), δ: 165.7, 165.1, 139.6, 132.0, 129.1, 129.0, 128.3, 126.6, 115.6, 54.1, 52.0, 39.6, 38.1, 29.8. IR(KBr) ν: 1726, 1649, 1438, 1277, 1249, 983, 702. HRMS(EI) (m/z): calcd for C16H15NO4 (M + H)+: 286.1074; found: 286.1070.

Methyl-1-cyano-2-((E)-3-ethoxy-3-oxoprop-1-en-1-yl)-3-phenylcyclopropane-1-carboxylate (6p)

A mixture of 2-cyanoacetate 5b (19.8 mg, 1 equiv.), (E)-(4-ethoxy-4-oxobut-2-en-1-yl)dimethylsulfonium bromide 3a (76.5 mg, 1.5 equiv.), Na2CO3 (42 mg, 2 equiv.), l-proline (2.3 mg, 0.1 equiv.) and benzaldehyde 2a (25.4 mg, 1.2 equiv.) in DCM. The reaction mixture was stirred at 0 °C overnight. The reaction mixture was concentrated in vacuo. The residue was purified by column chromatography (EA : PE, 1 : 5) to afford compound 6p as a white oil (44.9 mg, 75% yield), Rf = 0.16 (EtOAc/petroleum ether 1 : 10). 1H NMR (CDCl3, 400 MHz), δ: 7.42–7.36 (m, 3H), 7.30 (d, J = 6.8 Hz, 2H), 6.97–6.91 (m, 1H), 6.24 (d, 1H), 4.25–4.19 (m, 2H), 3.88 (s, 3H), 3.54 (d, J = 8.8 Hz, 1H), 3.07 (t, J = 9.2 Hz, 1H), 1.30 (t, J = 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3), δ: 165.3, 165.1, 139.3, 132.0, 129.1, 129.0, 128.3, 127.1, 115.6, 60.9, 54.1, 39.6, 38.2, 29.7, 14.3. IR(KBr) ν: 2245, 1712, 1649, 1438, 1277, 1242, 1179, 1123, 1032, 983, 695. HRMS(EI) (m/z): calcd for C17H17NO4 (M + H)+: 300.1230; found: 300.1232.

Ethyl-1-cyano-2-((E)-3-methoxy-3-oxoprop-1-en-1-yl)-3-phenylcyclopropane-1-carboxylate (6q)

A mixture of ethyl 2-cyanoacetate 5c (22.6 mg, 1 equiv.), (E)-(4-methoxy-4-oxobut-2-en-1-yl)dimethylsulfonium bromide 3b (72.3 mg, 1.5 equiv.), Na2CO3 (42 mg, 2 equiv.), l-proline (2.3 mg, 0.1 equiv.) and benzaldehyde 2a (25.4 mg, 1.2 equiv.) in DCM. The reaction mixture was stirred at 0 °C overnight. The reaction mixture was concentrated in vacuo. The residue was purified by column chromatography (EA : PE, 1 : 5) to afford compound 6q as a yellow oil (41.9 mg, 70% yield), Rf = 0.15 (EtOAc/petroleum ether 1 : 10). 1H NMR (CDCl3, 400 MHz), δ: 7.43–7.36 (m, 3H), 7.31–7.29 (m, 2H), 6.96 (dd, J1 = 15.6 Hz, J2 = 9.6 Hz, 1H), 6.24 (d, J = 15.6 Hz, 1H), 4.36–4.30 (m, 2H), 3.76 (s, 3H), 3.53 (d, J = 8.4 Hz, 1H), 3.06 (t, J = 8.8 Hz, 1H), 1.36 (t, J = 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3), δ: 165.6, 164.5, 139.7, 132.0, 129.0, 128.9, 128.2, 126.4, 115.5, 63.5, 51.9, 39.3, 38.0, 29.9, 14.1. IR(KBr) ν: 2925, 1733, 1649, 1508, 1284, 990, 702. HRMS(EI) (m/z): calcd for C17H17NO4 (M + H)+: 300.1230; found: 300.1234.

Conflicts of interest

There are no conflicts to declare.